Blood tests could replace biopsies by 2016

Dr. Bruce McManus says new procedures could help predict organ rejection and lead to personalized treatment - and save lives.Arlen Redekop, PNG
/ The Province

Gordon Allan describes the biopsies he has endured as 'very invasive, very traumatic'.Jason Payne, PNG
/ The Province

Dr. Dan Holmes of the PROOF Centre hopes to see prototypes of the new biomarker blood tests, which would replace biopsies, within one to 1½ years.Jason Payne, PNG
/ The Province

After Vancouver's Gordon Allan survived both a heart transplant and a kidney transplant, the last thing he wanted to do was to endure more medical procedures.

But to ensure his new organs weren't being rejected, he had to undergo a dozen heart biopsies within the first year - interventional procedures where tissue is removed from organs to test for immune rejection.

"It's very invasive, it's very traumatic," Allan, a 60-year-old fund manager, said of the procedures, performed via catheterization under mild sedation for hearts and under local anesthetic for kidneys.

Allan was born with a missing heart valve. A stopgap surgery in his 30s failed after about a decade. He was about to have a new heart procedure when he went into cardiac arrest and woke from a coma 11 days later with a new heart but failed kidneys. That meant dialysis and then a kidney transplant at St. Paul's courtesy of a donation from his sister. The medical interventions were life-saving, but since he's been well, Allan wondered if his follow-up care, specifically the biopsies, had to be so invasive.

"It seemed to me that there had to be a better way," he said.

Turns out, there is. Or will be soon.

Researchers at the Centre of Excellence for Prevention of Organ Failure (PROOF) are working on sophisticated new blood-based biomarker tests that could ultimately do away with the need for biopsies, replacing them with blood tests.

The PROOF Centre was founded in 2008 by competitive federal funding from the Networks of Centres of Excellence, a not-for-profit society hosted by Providence Health Care and UBC to develop new blood tests for kidney, lung and heart failure care, burdens that cost Canadian health care $35 billion a year. With new testing tools, the PROOF Centre team hopes to confirm and even predict organ rejection in a non-invasive manner. This could revolutionize post-transplant care around the world and save healthcare systems millions.

Diagnosis

PROOF Centre chief scientific officer Dr. Scott Tebbutt stands in a bright and lacquered-white laboratory in a crisp white lab coat. Here, Tebbutt and his fellow scientists are racing to perfect a new generation of post-transplant diagnostic tools.

"About 10 per cent of patients have acute kidney rejection," said Tebbutt, a UBC associate professor of medicine. "The problem is you can only spot it once it's happening, and tissue damage is under way. That's the trouble with biopsy. And patients hate it. It's invasive and expensive. We're trying to replace it with a blood test."

It's no easy task. Nor is explaining the science behind it.

So PROOF Centre founding director Dr. Bruce McManus suggests likening test results to patterns or signatures that, when compared among organ rejectors, non-rejectors and control groups, provide a distinctive signal when a rejection is imminent or likely in future.

"Like your signature on paper, it's your signature ... who you are at that time in your illness and it says whether you are having rejection or not," he said.

In simplified terms, the tests work by evaluating proteins and messenger RNA in the blood. There are tens of thousands of mRNA signals and some 2,000 proteins that could be compared, so a large part of the PROOF Centre's work has been selecting the best and reducing down to 10 to 20 biomarkers.

They've compared patterns across cohorts of patients at St. Paul's, other Canadian hospitals and in Australia and India, to ensure they work accurately across populations. And they do.

The next step is to launch clinical studies, hopefully starting in 2013. They'll ultimately seek approval from Health Canada and the FDA and collaborate with industry partners to commercialize the test. Initial economic models show Canada could save $17 million over five years once the kidney transplant test is in clinical use.

Sales of the test in the U.S. and globally would generate resources for UBC and the PROOF Centre to sustain future biomarker research.

Transplant centres already have the platform needed to process the blood-based rejection test. If all goes well, McManus said, by 2016, patients could choose a blood test over a biopsy.

"We're bringing these biomarkers from an idea all the way to a clinic. It's not far off," said Dr. McManus, who is also a professor at UBC's department of pathology and laboratory medicine. "The purpose is to move research into action," he added. "The idea is to save money and enhance patient experience by reducing invasiveness of care, while creating wealth."

One selling point? Armed with blood test rejection confirmations or predictions doctors could tailor the level of immuno-suppressant drugs to each individual. In effect: personalized medicine. Those with little chance of failure would need fewer drugs, saving money and reducing adverse effects, and those who could fail would be put on a stricter regimen to help prevent rejection, saving more organs - and lives.

Factory efficiency

In a different part of St. Paul's, Dr. Dan Holmes, PROOF Centre medical officer for the clinical laboratory, strides through another lab: this one more like a busy factory floor than the spare PROOF Centre environs.

Here in the medical laboratories, more than 2 million diagnostic tests are performed each year. Staffers track hundreds of samples, running some through machines that process up to 1,800 tests per hour, others through equipment that costs almost three-quarters of a million dollars.

It's here Holmes expects to run the PROOF Centre's tests in future. With the help of an in-house research scientist, the lab has already developed 14 other unique diagnostic tests for various conditions over the past two years. But the organ rejection test would be a game-changer, Holmes said, with system-wide implications across Canada and abroad.

"There is no blood test now to predict who is going to reject an organ in the future," Holmes explained, but it's the PROOF Centre's intention to create one - and fast.

"I'd like to see clinically functioning prototype tests in one to 1½ years," he said. "My job will be overseeing the validation of the tests to see if they work."

Allan, the transplant recipient, has faith that it will work and that this new blood test will save other transplant patients from having to undergo as many biopsies as he did. To that end, he serves as a community leader and patient advocate on one of the PROOF Centre's advisory boards.

"I am the only person sitting at the table who has had a biopsy," he said of his vested interest in the development of the blood test.

"We've all had blood tests, it's nothing ... [replacing biopsies with blood tests] for the patient and for the system, it's huge."

EVOLUTION IN PATIENT CARE

. 1962 St. Paul's became a B.C. centre for dialysis, as Dr. Russell Palmer, the first in North America to treat patients with the artificial kidney machine, joined.

. 1965 An artificial kidney machine, only the third in Vancouver, was donated by the Vancouver South Lions Club.

. 1968 New renal unit opens, with 12 artificial kidney machines. Staff also begin training patients to do hemodialysis themselves at home, a first in B.C.

. 1985 B.C. Transplant formed to help increase the donation and availability of organs for transplant.

. 1986 The hospital performs its first kidney transplant on a father of two, a millworker from Prince Rupert.

. 20 03 By this date, St. Paul's performed over 75 kidney transplants a year. Today, it performs about 100.

. 2008 The Centre for Excellence for Prevention of Organ Failure was founded to develop blood tests to replace biopsies to improve heart, lung and kidney failure care.

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